Pancreatic islets of Langerhans are constituted by cells that rarely undergo through mitosis and that exhibit poor capability of regeneration after injury. Recently, Terazono et al. isolated and characterized a cDNA from regenerating pancreatic derived library, designated reg (for regenerating gene). Reg mRNA levels were shown to be markedly elevated in islets induced to proliferate by pancreatectomy and nicotinamide treatment. The increase in expression of REG gene was temporally correlated with the increase in size of regenerating islets and the decrease of glycosuria. Increase in reg mRNA has also been demonstrated in the hyperplastic islets of the NON mice after treatment with aurothiaglucose. In addition, it has been shown that the implantation of a solid insulinoma tumor into rats caused a dramatic reduction of the islets volume as well as of the function of endogenous islet ~-cells. This phenomenon was associated with a coordinate suppression of both reg and insulin gene expression. When removal of the tumor was performed, this resulted in a rapid proliferation of the endocrine ~-cells and it caused an induction of reg expression and the restoration of the endogenous insulin gene expression. All of those experimental maneuvers show an intriguing correlation between reg gene expression and changes in ~-cell mass or ~-cell function. We hypothesize that REG may be a crucial autocrine and/or paracrine growth factor during embryogenesis as well as for maintenance of ~-cell function in the adult. We believe that alterations of the REG gene expression may be involved in the progressive ~-cell dysfunction with aging and diabetes. We plan to use molecular techniques to measure mRNA levels of REG in the pancreas of rodents during the normal aging process, and in rodent strains with genetic forms of type I or type II diabetes.